Comparison 1. Heated tobacco product (HTP) use compared with cigarette smoking.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Adverse events	6	1713	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.92, 1.15]
1.2 Serious adverse events	9	2009	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.33, 1.94]
1.3 1‐Hydroxypyrene (1‐OHP)	10	1960	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐0.67, ‐0.17]
1.3.1 Intention‐to‐treat	4	1154	Mean Difference (IV, Random, 95% CI)	‐0.58 [‐0.94, ‐0.21]
1.3.2 Per‐protocol	6	806	Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.68, 0.05]
1.4 1‐Naphthol	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.4.1 Per‐protocol	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.5 2‐Naphthol	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.5.1 Per‐protocol	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.6 Exhaled carbon monoxide (CO)	3	1322	Mean Difference (IV, Random, 95% CI)	‐9.13 [‐10.49, ‐7.78]
1.6.1 Intention‐to‐treat	1	858	Mean Difference (IV, Random, 95% CI)	‐6.20 [‐11.01, ‐1.39]
1.6.2 Per‐protocol	2	464	Mean Difference (IV, Random, 95% CI)	‐9.37 [‐10.73, ‐8.01]
1.7 Carboxyhaemoglobin (COHb)	9	1807	Mean Difference (IV, Random, 95% CI)	‐0.74 [‐0.97, ‐0.52]
1.7.1 Intention‐to‐treat	4	1154	Mean Difference (IV, Random, 95% CI)	‐0.92 [‐1.44, ‐0.41]
1.7.2 Per‐protocol	5	653	Mean Difference (IV, Random, 95% CI)	‐0.61 [‐0.82, ‐0.40]
1.8 3‐Hydroxypropylmercapturic acid (3‐HPMA)	10	1960	Mean Difference (IV, Random, 95% CI)	‐0.40 [‐0.62, ‐0.17]
1.8.1 Intention‐to‐treat	4	1154	Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.28, ‐0.11]
1.8.2 Per‐protocol	6	806	Mean Difference (IV, Random, 95% CI)	‐0.53 [‐0.94, ‐0.13]
1.9 Monohydroxy‐3‐butenyl mercapturic acid (MHBMA)	10	1960	Mean Difference (IV, Random, 95% CI)	‐1.15 [‐1.52, ‐0.78]
1.9.1 Intention‐to‐treat	4	1154	Mean Difference (IV, Random, 95% CI)	‐0.75 [‐1.06, ‐0.43]
1.9.2 Per‐protocol	6	806	Mean Difference (IV, Random, 95% CI)	‐1.41 [‐1.95, ‐0.87]
1.10 4‐(Methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL)	10	1959	Mean Difference (IV, Random, 95% CI)	‐0.81 [‐1.07, ‐0.55]
1.10.1 Intention‐to‐treat	4	1154	Mean Difference (IV, Random, 95% CI)	‐0.72 [‐1.05, ‐0.38]
1.10.2 Per‐protocol	6	805	Mean Difference (IV, Random, 95% CI)	‐0.89 [‐1.32, ‐0.45]
1.11 Forced expiratory volume in 1 second (FEV1)	5	1290	Mean Difference (IV, Random, 95% CI)	0.02 [0.00, 0.03]
1.11.1 Intention‐to‐treat	1	858	Mean Difference (IV, Random, 95% CI)	0.01 [0.00, 0.03]
1.11.2 Per‐protocol	4	432	Mean Difference (IV, Random, 95% CI)	0.02 [‐0.00, 0.04]
1.12 Systolic blood pressure	3	288	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.02, 0.02]
1.12.1 Per‐protocol	3	288	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.02, 0.02]
1.13 Diastolic blood pressure	3	288	Mean Difference (IV, Random, 95% CI)	‐0.00 [‐0.03, 0.03]
1.13.1 Per‐protocol	3	288	Mean Difference (IV, Random, 95% CI)	‐0.00 [‐0.03, 0.03]
1.14 Forced vital capacity (FVC)	2	196	Mean Difference (IV, Random, 95% CI)	‐0.12 [‐0.45, 0.21]
1.14.1 Per‐protocol	2	196	Mean Difference (IV, Random, 95% CI)	‐0.12 [‐0.45, 0.21]